Tissue graft constructs, such as regenerative scaffolds, are commonly utilized in tissue engineering applications to repair, replace, restore and/or remodel damaged or diseased tissue. These tissue scaffolds often include matrices, for example, a naturally occurring extracellular matrix (ECM), to provide structure to the scaffold. Naturally occurring ECM is a mixture of structural and functional molecules arranged within a complex three-dimensional ultrastructure that surrounds and supports cells that are found within tissues and organs. Alternatively, a matrix may be manufactured from structural or functional components of a naturally occurring ECM, such as collagen. Naturally occurring ECMs are composed of both structural and functional biologically active molecules, including cytokines and growth factors, which play an important role in replication, differentiation, maturation and organization of cells in contact with the matrix.
The composition and structure of a naturally occurring ECM is a function of age of the host, location of the ECM within specific tissues and organs, and the demands placed upon the ECM as a result of environmental stressors. For example, naturally occurring musculotendinous ECM becomes stronger as a result of collagen deposition and collagen fiber reorganization in response to repeated uniaxial or multiaxial stress or compressive loading. Naturally occurring hepatic ECM shows increased concentration of laminin, fibronectin and collagen IV within hours of the onset of hypoxia. The naturally occurring ECM has been recognized as a critical component in the host response to tissue injury just as it is an essential element of normal tissue development.
Selected forms of the naturally occurring ECM, for example, ECM derived from the small intestinal submucosa (SIS), have been successfully used as a scaffold for tissue engineering applications in both pre-clinical animal studies and in human clinical applications. Experience with patients has suggested that the degree of success and the morphologic changes that occur within the scaffold over time are a direct result of local environmental stimuli, such as mechanical loading (rehabilitation), the viability of surrounding tissue, and the surrounding tissue pH and ionic concentrations. Although these scaffold compositions have provided a starting point for tissue engineering applications, there exists a need in the art for compositions that have improved ability to support the replication, differentiation, maturation and spatial organization of numerous cell types.